U.S. Pat. No. 5,661,151 discloses posaconazole and its use as antifungal agent with a broad spectrum of activity. In vitro and in vivo studies demonstrated that posaconazole has good activity against Candida species (including albicans, glabrata, and tropicalis), as well as other opportunistic fungi, including but not limited to, Aspergillus, Fusarium, Basidiomycetes, Blastomyces, Coccidioides, Histoplasma, Zygomycetes, and Scedosporium, and opportunistic monilaceous and dematiaceous molds and dermatophyte. Posaconazole, however, is very insoluble, (water solubility <0.002 mg/mL). Therefore, it has been a challenge to provide intravenous or parenteral formulations having desirable pharmacologic properties.
Commonly-assigned U.S. Pat. No. 5,965,566 discloses releasable PEG conjugates of various anticancer agents using ester-based linkages. The prodrug conjugates are designed with various bifunctional spacers inserted between the PEG and parent compound to be released. These bifunctional spacers are believed to play a role in the modulation of the hydrolysis reaction which frees the parent compound in vivo. In certain examples, a diglycolic-acid based spacer is used. Details are described in FIG. 2 therein. The contents of the '566 patent are incorporated herein by reference.
In spite of the prior work in this regard, there continues to be a need for improved posaconazole compositions and methods of treatment using the same. The present invention addresses these needs.